Glycochemistry is a domain of organic chemistry involving specific synthetic and characterization methodologies. Based on complex and plural retrosynthetic schemes, glycochemistry and its numerous applications in glycobiology remain emergent compared to Proteomic and Genomic approaches. Our laboratory possesses the following skills: oligosaccharide synthesis, sulfur or nitrogen containing analogues synthesis, selective modification of mono-, oligo- and polysaccharides from biomass, modification of cyclodextrins, and the study of sugar-protein interactions and supramolecular selfassembly. The laboratory is also integrated in national and international networks related to glycosciences (GFG, EPNOE, etc…)
The scientific project will be based on the synthesis of new glycosidic analogues for chemobiology applications in a general way (i.e. sugar-protein interactions) and the development of corresponding analytical tools and methodology. The project must be based on biosourced platform molecules obtained by respecting the concepts of green/sustainable chemistry. Biological tests and interaction studies at the molecular level will be performed at LG2A or through external collaborations.
The selected applicant will be in charge of organic chemistry courses in the Licence (Bachelor) in Chemistry and in the Master in Chemistry, specialized in « Chimie Durable-Organique » (Sustainable Organic Chemistry) and in « Analyse, Contrôle-Qualité » (Analysis, Quality Control) at the Université de Picardie Jules Verne (UPJV). He/she will participate in the different courses of organic synthesis, supramolecular chemistry, characterization techniques as NMR, chromatography and/or mass spectrometry. He/she will take part in the creation of new teaching modules in different levels (Bachelor, Master, PhD) related to the MAIA project (artificial intelligence) on synthetic and supramolecular chemistry aspects. He/she will be involved in the responsibility of a year and/or a specialization.
Moumene, T.; Kadari, M.; Belarbi, E.-h.; Boudali, N.; Said Benyahia, M.; Nguyen Van Nhien, A.; Dupont, L.; Bresson, S.
In this work, we make a comparative study between ZnO nanoparticles samples (NPs) synthesized by the conventional method (ZnO-S) and samples elaborated in an ionic liquid (IL) media (ZnO-IL) to see the effect of the latter on the structural, optical and morphological properties of these NPs. The results of this study are obtained using the following characterization methods: X-ray diffraction for the study of the structural properties of the different ZnO NPs samples, infrared spectroscopy (FTIR) to determine the nature of the different bonds present in our samples, UV–Visible spectrometry to determine the gap energy of zinc oxide. The results of Transmission Electron Microscopy have also been reported to show the effect of ionic liquid on the morphology of ZnO NPs. The XRD allowed us to see the effect of ionic liquid on the size of the crystallites manifested by a noticeable decrease. The curves of the UV–Vis show that the value of the gap energy is not the same for the two samples of ZnO-S and ZnO-IL, which implies that the latter has been influenced by the change in the reaction media. Transmission electron microscopy shows that the ionic liquid influences the size of the nanoparticles, there are two populations of nanoparticles, the first between (50 and 100 nm) as for ZnO-S NPs and a second in the order of 20 nm, which implies that the presence of the ionic liquid reduced the size of the NPs. We conclude that ionic liquid can be very useful to control the size of ZnO NPs and the appearance of novel properties.
Roux, M.; Legrand, F. X.; Bil, A.; Bonnet, V.; Djedaini-Pilard, F.
Small bilayer lipid aggregates such as bicelles provide useful isotropic or anisotropic membrane mimetics for structural studies of biological membranes. We have shown previously by deuterium NMR that a wedge-shaped amphiphilic derivative of trimethyl betacyclodextrin anchored in deuterated DMPC-d27 bilayers through a lauryl acyl chain (TrimbetaMLC) is able to induce magnetic orientation and fragmentation of the multilamellar membranes. The fragmentation process fully detailed in the present paper is observed with 20% cyclodextrin derivative below 37 degrees C, where pure TrimbetaMLC self-assembles in water into large giant micellar structures. After deconvolution of a broad composite (2)H NMR isotropic component, we propose a model where the DMPC membranes are progressively disrupted by TrimbetaMLC into small and large micellar aggregates depending whether they are extracted from the outer or inner layers of the liposomes. Below the fluid-to-gel transition of pure DMPC-d27 membranes (T(c) = 21.5 degrees C), the micellar aggregates vanish progressively until complete extinction at 13 degrees C, with a probable release of pure TrimbetaMLC micelles leaving lipid bilayers in the gel phase doped with only a small amount of the cyclodextrin derivative. Bilayer fragmentation between T(c) and 13 degrees C was also observed with 10% and 5% of TrimbetaMLC, with NMR spectra suggesting possible interactions of micellar aggregates with fluid-like lipids of the P(beta') ripple phase. No membrane orientation and fragmentation was detected with unsaturated POPC membranes, which are able to accommodate the insertion of TrimbetaMLC without important perturbation. The data are discussed in relation to the formation of possible DMPC bicellar aggregates such as those known to occur after insertion of dihexanoylphosphatidylcholine (DHPC). These bicelles are in particular associated with similar deuterium NMR spectra exhibiting identical composite isotropic components which were never characterized before.
Ferreira Funes, C.; Bouvier, B.; Cézard, C.; Fuentealba, C.; Jamali, A.; Courty, M.; Hadad, C.; Nguyen Van Nhien, A.
Chitin nanocrystals have gained growing interest due to their many excellent properties, however the higher crystallinity of these nano-rod-shaped particles is a major hindering factor in preparation of nanochitosans with low degree of acetylation (DA). Here we studied the effect of the ionic liquid 1-ethyl-3-methylimidazolium acetate (IL) and deep eutectic solvent (choline chloride:lactic acid) (DES) pretreatments of chitin nanocrystals (NCChits) before the deacetylation step using both experimental and theoretical approaches. The results showed that the ionic liquid pretreatment was able to partially disrupt the crystalline structure leading to a lower DA (18.2 %) after two cycles of deacetylation reaction. DES pretreatment, however, was unable to disturb the intra- and intermolecular hydrogen bonds, resulting in a DA of 73.6 % similar to that of unpretreated chitin nanocrystals (73.2 %). SEM images of chitin nanocrystals pretreated with ionic liquid showed that the crystals can rearrange into sheets. Molecular simulations reveal the detailed mechanism of chitin nanocrystal dissociation, in which the combination of a net molecular charge and hydrogen-bonding groups on a single scaffold (as is the case for [C2mim] and [OAc]) plays a paramount role. These results can open the way to afford controlled nanochitosan sheets from chitin nanocrystals.
Rigaud, S.; Dosso, A.; Lesur, D.; Cailleu, D.; Mathiron, D.; Pilard, S.; Cezard, C.; Djedaini-Pilard, F.
When working on the synthesis of substituted cyclodextrins (CDs), the main challenge remains the analysis of the reaction media content. Our objective in this study was to fully characterise a complex isomers mixture of Lipidyl-betaCDs (LipbetaCD) obtained with a degree of substitution 1 (DS = 1) from a one-step synthesis pathway. The benefit of tandem mass spectrometry (MS/MS) and ion mobility separation hyphenated with mass spectrometry (IM-MS) was investigated. The MS/MS fragment ion's relative intensities were analysed by principal component analysis (PCA) to discriminate isomers. The arrival time distribution (ATD) of each isomer was recorded using a travelling wave ion mobility (TWIM) cell allowing the determination of their respective experimental collision cross section (CCSexp). The comparison with the predicted theoretical CCS (CCSth) obtained from theoretical calculations propose a regioisomer assignment according to the betaCD hydroxyl position (2, 3, or 6) involved in the reaction. These results were validated by extensive NMR structural analyses of pure isomers combined with molecular dynamics simulations. This innovative approach seems to be a promising tool to elucidate complex isomer mixtures such as substituted cyclodextrin derivatives.
Vuillemin, M. E.; Waterlot, C.; Verdin, A.; Laclef, S.; Cézard, C.; Lesur, D.; Sarazin, C.; Courcot, D.; Hadad, C.; Husson, E.; Van Nhien, A. N.
This study aims to investigate the ability of an imidazolium biobased Zwitterionic Ionic Liquids (ZILs) in enhancing the phytoavailability of copper from garden (G) and vineyard (V) soils using the model plant ryegrass. Uncontaminated and artificially contaminated CuSO4 soils, unamended and ZIL-amended soil modalities were designed. The copper/ZIL molar ratio (1/4) introduced was rationally established based on molecular modeling and on the maximal copper concentration in artificially contaminated soil. Higher accumulation of copper in the shoots was detected for the uncontaminated and copper contaminated ZIL amended V soils (18.9 and 23.3 mg.kg−1, respectively) contrary to G soils together with a ZIL concentration of around 3% w/w detected by LC-MS analyses. These data evidenced a Cu-accumulation improvement of 38 and 66% compared to non-amended V soils (13.6 and 13.9 mg.kg−1 respectively). ZIL would be mainly present under Cu(II)-ZIL4 complexes in the shoots. The impact on the chemical composition of shoot were also studied. The results show that depending on the soils modalitity, the presence of free copper and/or ZIL led to different chemical compositions in lignin and monomeric sugar contents. In the biorefinery context, performances of enzymatic hydrolysis of shoots were also related to the presence of both ZIL and copper under free or complex forms. Ecotoxicity assessment of the vineyard soil samples indicated that the quantity of copper and ZIL remaining in the soils had no significant toxicity. ZIL amendment in a copper-contaminated soil was demonstrated as being a promising way to promote the valorization of phytoremediation plants.
Ndour, M.; Bonnet, J.-P.; Cavalaglio, S.; Lombard, T.; Courty, M.; Aymard, L.; Przybylski, C.; Bonnet, V.
The semi-synthetic polysaccharide carboxymethylcellulose (CMC) is one of the most studied and effective polymer binders for silicon-based anodes in Li-ion batteries. The formulation of the corresponding composite negative electrode with an appropriate mixture of electroactive silicon, a CMC binder and a carbon additive is mandatory to ensure a good electrical conductivity. Blending is commonly realized by a highly energetic ball milling treatment of these three aforementioned components. This type of mixing reduces the size of the obtained particles and can also potentially agglomerate them. Morever, it allows the formation of a nanostructured mixture which is essential for both the silicon activation and to achieve good electrochemical performance. However, such strong treatment can also cause a significant degradation of the polymer chains, as we have recently demonstrated for polyacrylic acid (PAA). In the present work, the structural and chemical effects of this mechanical grinding on three commercial CMCs ranging from 90 to 700 kg mol−1 were investigated. All the polymers were characterized using SEC-MALLS, FTIR spectroscopy, MALDI-TOF mass spectrometry and TGA-MS thermal analysis. In all cases, a huge average molecular weight decrease was noticed, leading to the appearance of a bimodal distribution with low (52–72 kg mol−1) to very low molecular weight populations (1–1.8 kg mol−1). From these results, two formulations of a negative electrode were compared, one with ball milling of the three compounds and another one including only ball milling steps for silicon and carbon. After the correlation of the characteristics of this negative electrode composite with the electrochemical results, it was demonstrated that a high number of functions for supramolecular or covalent linkages are keypoints of the herein anode performance. Low molecular weight CMC derivatives (about 64 kg mol−1) obtained by ball milling treatment led to higher stability of the electrode.
The scientific project will be based on the synthesis of new glycosidic analogues for chemobiology in a general way, and more specifically for the study of sugar-protein interactions and/or the development of corresponding analytical tools and methodology. The project must be based on biosourced plateform molecules respecting the concepts of green/sustainable chemistry. For example, target compounds able to achieve selective inhibition of enzymes involved in carbohydrates biosynthesis or metabolism (glycosidases, glycosyltransferases). In this context, the project could involve the synthesis and biological evaluation of new inhibitors like S-, N-, or C-glycosidic analogues, in order to target bacterial enzymes or enzymes related to some diseases as the α-glucosidase (diabetes of type II) or heparanase (cancer metastasis). Proposals involving others aspects of glycochemistry and the study of sugar-protein interactions and supramolecular assemblies, or still methods of structural analysis, can also be envisaged.
Le projet scientifique reposera sur la synthèse d’analogues glycosidiques originaux dans le cadre de la chemobiologie de façon générale et plus spécifiquement pour l’étude des interactions sucre-protéine et/ou le développement des méthodes analytiques correspondantes. Le projet doit être basé sur des molécules plate-forme biosourcées respectant autant que possible les concepts de la chimie verte/durable. A titre d’exemple, on peut envisager des composés cibles capables d’inhiber sélectivement les enzymes impliquées dans la biosynthèse ou le métabolisme des glucides (glycosidases, glycosyltransferases). Dans ce cadre, le projet pourra impliquer la synthèse et l’évaluation biologique de nouveaux inhibiteurs de ces enzymes, comme par exemple des analogues S-, N-, ou C-glycosidiques, afin de cibler par exemple des enzymes bactériennes ou celles impliquées dans le développement de certaines maladies comme l’α-glucosidase (dans le diabète de type II) ou l’héparanase (dans la métastase de cancers). Des propositions concernant d’autres aspects de la glycochimie, ainsi que l’étude des interactions sucre-protéine et des assemblages supramoléculaires, ou encore des méthodes d’analyse structurale, seront également envisageables.
Rudtanatip, T.; Somintara, S.; Sakaew, W.; El-Abid, J.; Cano, M. E.; Jongsomchai, K.; Wongprasert, K.; Kovensky, J.
Abstract Sulfated galactans (SG) isolated from Gracilaria fisheri was partially degraded (DSG), and subsequentially supplemented with octanoyl (DSGO) and sulfate (DSGS) groups. The molecular weights of DSG, DSGO, and DSGS were 7.87, 152.79, and 97.07?kDa, respectively. The modification was confirmed using FTIR and NMR, whilst in vitro wound healing activity was assessed using scratched wound fibroblasts. The results revealed that DSGO exhibited highest percentage of wound closure in scratched fibroblast L929 cells. Furthermore, DSGO was able to promote proliferation and accelerate migration of scratched fibroblasts, which corresponded to the regulation of proteins and mRNA (Ki67, p-FAK, vimentin and E-cadherin) determined by Western blotting and qPCR analysis. The superior wound healing activity of DSGO was also confirmed in excision wound of rats. The results demonstrated that DSGO significantly enhanced the percentage of wound closure, re-epithelialization, and collagen arrangement, increased α-SMA and vimentin expression, and decreased that of TNF-α at the wound site. The results suggest that degraded SG supplemented with medium-chain fatty acids of octanoyl group might pass through the membrane, subsequently activating the mediators associated with proliferation and migration of fibroblasts, which could potentially lead to the promotion of wound healing activity. This article is protected by copyright. All rights reserved
Przybylski, C.; Bonnet, V.
In this study, the size and shape of supramolecular assemblies between cyclo-oligosaccharides and proton, ammonium or a series of alkali metals by electrospray coupled to trapped ion mobility-mass spectrometry (ESI-TIMS) have investigated. Native cyclodextrins (CD) were selected as models, and collision cross section (CCS) values were deducted for the main positive singly and doubly charged species. Experimental CCS values were in good agreement with those obtained from molecular modeling. Due to the high mobility resolving power and resolution, it was possible to highlight the presence of various conformers. Also, TIMS allowed to discriminate and estimate the content of various orientations from non-covalent nanotubes-based CD, involving secondary/secondary rim hydroxyl groups (head-to head), primary/secondary rim (head-to-tail) hydroxyl groups or primary/primary rim (tail-to-tail) hydroxyl groups interactions. Such results pave the way for a better knowledge of the topology of cyclo-oligosaccharides based supramolecular complexes, demonstrating that TIMS can be a particularly attractive molecular descriptor.
